As a result of their high surface area, large pore volume and/or pore size selectivity, porous polymer materials have found wide application in many technological fields. For example, porous polymers may be used as separation or filtration materials, as absorbent materials and as scaffolds for catalysis, immobilisation of pharmaceutical compounds or biological molecules and tissue engineering.
The pore morphology of a porous polymer will often be a critical parameter in determining its suitability for use in a given application. For separation and filtration technologies, pore size is fundamental to achieving the desired degree of filtration or separation. However, in the case of tissue engineering applications, polymers having pores of an appropriate size alone are generally not sufficient for tissue regeneration. In particular, it has been demonstrated that controlling internal pore architecture such as connectivity and orientation is crucial to controlling the vascularisation and mechanical properties of regenerate tissue. In some applications, it is also important that the porous polymer replicate a complex shape. Accordingly, the ability to control the porous polymer architecture through design and fabrication is often very important to the successful application of these materials.
Numerous techniques for preparing porous polymers which afford varying degrees of control over design and fabrication have been developed. Techniques known in the art include textile processing through crimping, cutting and needling, fibre bonding, electrospinning, solvent casting/particulate leaching (SCPL), thermally induced phase separation (TIPS), gas or blowing agent foaming and rapid prototyping (RP). Of these techniques, textile processing, fibre bonding and electrospinning can produce highly porous and interconnected fibre structures. However, these structures typically have poor mechanical strength.
SCPL techniques have been used to produce porous three dimensional foam structures, and offer relatively good control over pore size and porosity. However, structures produced by this technique are generally limited to membranes having a thickness of no greater than 3 mm, and the pores are generally of an irregular shape and are poorly interconnected.
Gas and blowing agent foaming techniques are technically simple and can be used with a diverse array of polymers, but the resulting porous foam will generally have a closed pore structure and hence poor interconnectivity. On the other hand, RP techniques can produce highly porous and fully interconnected polymer structures, and offer an accurate degree of control over pore size and pore shape. However, the range of polymers suitable for use in RP techniques is limited, and the equipment required to perform the technique is very expensive.
TIPS has been shown to be a particularly effective technique for producing porous polymer structures. This technique has traditionally made use of thermal energy as a driving force to induce phase separation. In performing the technique, a polymer is typically dissolved in a solvent or solvent/non-solvent mixture, and solid-liquid or liquid-liquid phase separation is then induced by lowering the solution temperature. The phase separation results in polymer-rich and polymer-poor phases being formed within the solution. After solidifying one or both of the polymer-rich or polymer-poor phases, the polymer-poor phase is removed leaving a highly porous polymer structure.
TIPS has a number of advantages over other techniques for preparing porous polymer structures. The technique is relatively simple to apply and can be performed at relatively low cost. The morphology of the porous polymer structures can be tailored to some extent through variation of processing parameters such as polymer concentration, solvent/non-solvent type, solvent/non-solvent ratios and thermal quenching strategies such as quenching temperature and quenching rate. The technique is also suitable for use with a diverse array of polymers and demonstrates the capability to produce porous polymers with complex shapes, large size and thick structures.
A notable advantage of TIPS is that it can be used to prepare porous polymers with good interconnectivity of the pores. An interconnected pore morphology is desirable in many applications, for example in tissue engineering applications. In particular, desirable characteristics of polymer structures used in tissue engineering include a highly open porous and interconnected architecture with controlled pore size, porosity, pore shape, and alignment to facilitate oxygen, nutrient, and waste transfer as well as rapid, controlled vascularisation and tissue ingrowth.
In conducting TIPS, cooling parameters for the polymer solution play an important role in determining the morphology of the resultant porous polymer structure. During cooling of a polymer solution, solid-liquid phase separation can occur as a result of solvent freezing or polymer precipitation. A non-solvent may be included in the polymer solution to promote liquid-liquid phase separation. FIG. 1 represents a typical polymer solution phase diagram for a polymer-solvent/non-solvent system at a nominal polymer concentration. The Y-axis defines temperature, with T2 representing the glass transition temperature of the polymer and T3 the solidification temperature of the solvent. These temperatures correspond to solid-liquid phase separation. The X-axis defines the solvent/non-solvent composition, with S1 representing the solvent and S2 representing the non-solvent.
The upper and lower parabolic-like curves in FIG. 1 are known as the binodal and spinodal curves, respectively. In regions defined above the binodal curve, the polymer solution exists as a stable single-phase system, whereas in regions below the binodal curve the polymer solution exists as a metastable or unstable two-phase system. In particular, the spinodal curve demarcates the two-phase region into metastable and unstable regions, with the metastable region being defined between the binodal and spinodal curves, and the unstable region being defined below the spinodal curve. The point Uc on the curves represents the maximum temperature at which spinodal decomposition may occur.
When the temperature of a polymer solution is reduced such that it passes from the single-phase region into the two-phase region, the solution may undergo phase separation by a nucleation and growth mechanism in the metastable region, or a spinodal decomposition mechanism in the unstable region. FIG. 1 illustrates the morphology of the two-phase separated systems that form through each phase separation mechanism. In particular, the nucleation and growth mechanism, which occurs in the metastable region, provides for spheroidal domains, whereas the spinodal decomposition mechanism, which occurs in the unstable region, provides for bi-continuous domains that give rise to interconnected pores.
The final morphology of a porous polymer structure formed by TIPS can be “fixed” by quenching the two-phase structure-formed composition to a temperature either below the glass transition temperature of the polymer (T2 in FIG. 1) and/or below the freezing temperature of the solvent (T3 in FIG. 1). Solvent/non-solvent can then subsequently be removed from the “fixed” porous polymer structure by sublimation, evaporation or solvent extraction under appropriate conditions.
Although it is possible to promote spinodal decomposition using TIPS to form porous polymer structures having an interconnected pore morphology, there are some limitations and disadvantages associated with doing so.
Referring again to FIG. 1, φ2 defines the solubility limit of a polymer at a specific solvent composition, whereby the polymer is substantially insoluble in solvent compositions to the left of the limit, but soluble enough to form a solution in solvent compositions to the right of the limit. Accordingly, when employing TIPS the viable operating region may be restricted to those solvent compositions which fall to the right of a solubility limit.
FIG. 1 also depicts a typical quenching regime which involves quenching the composition of the polymer solution defined at point X to point Y. Such a quenching regime will afford a porous polymer structure having a morphology which is at least in part derived through a spinodal decomposition mechanism. By this route, the polymer solution will generally first be heated to temperature T1 to provide for a single-phase polymer solution. The solution is then cooled to temperature T4, and in doing so passes through the metastable region (defined between the binodal and spinodal curves) and into the unstable region (defined below the spinodal curve). Under this regime, the cooling rate will be the dominant factor in determining the operative phase separation mechanism, and hence also the resulting morphology of the porous polymer structure. If the cooling rate is sufficiently fast, the polymer solution can quickly pass through the metastable region and into the unstable region, where phase separation will be dominated by a spinodal decomposition mechanism. In contrast, if the cooling rate is relatively slow, the solution may have enough time to form nuclei in the metastable region and phase separation may be dominated by a nucleation and growth mechanism. Accordingly, the temperature range defined by ΔT1 can also influence the operative phase separation mechanism. That is, where ΔT1 is large in passing from point X to point Y, the likelihood of at least some phase separation occurring by a nucleation and growth mechanism increases.
An important feature to note from FIG. 1 is that within the viable operating window defined to the right of the solubility limit φ2, much of the metastable region and all of the unstable region is located at temperatures below the glass transition temperature of the polymer and the freezing temperature of the solvent (i.e. T2 and T3). This is a common feature of phase diagrams for many polymer-solvent/non-solvent systems. In preparing porous polymer structures having an interconnected pore morphology, such a feature presents a number of disadvantages and limitations. One disadvantage is that in order to promote spinodal decomposition, the polymer solution will need to be rapidly quenched to very low temperatures, typically below −100° C. using liquid nitrogen. This adds complexity to performing TIPS, particularly on a large scale, and also adds considerable expense to the process.
Furthermore, a consequence of spinodal decomposition occurring at temperatures below the glass transition temperature of the polymer and/or the freezing point of the solvent is that to promote bi-continuous phase separation the polymer solution must be rapidly quenched into the unstable region so that it becomes supercooled. However, it will be appreciated that in such a supercooled state, the composition is thermodynamically unstable and will rapidly solidify. Accordingly, the ability to vary the morphology of the bi-continuous phase separated composition, and hence the morphology of the resulting porous polymer structure, through aging or annealing is minimal at best. Porous polymer structures having a bi-continuous morphology formed by TIPS are therefore prone to having small pore sizes.
It would therefore be desirable to develop a method that could be used to produce porous polymer structures having interconnected pore morphology which is less reliant upon the need to quench polymer solutions to very low temperatures, and which provides a greater opportunity to tailor the pore morphology of the porous polymer structures.